Stroke is the third leading cause of death and the main cause of permanent morbidity in the United States, affecting over 450,000 patients annually1. Recent studies in a murine model of ischemic stroke demonstrated a pivotal role for platelets in progressive microvascular thrombosis distal to the primary obstruction of a major cerebrovascular tributary2. This progressive microvascular thrombosis is characterized by distal platelet and fibrin accumulation, resulting in postischemic hypoperfusion (“no re-flow”) and neuronal injury2. While leukocyte adhesion receptors and recruited neutrophils contribute to postischemic hypoperfusion, postischemic hypoperfusion cannot be completely abrogated because even in the absence of neutrophils, progressive microvascular thrombosis persists3,4. Two thrombolytic agents, recombinant tissue-type plasminogen activator (rtPA) and pro-urokinase, have been used for treatment of stroke. However, their therapeutic utility is limited due to risk of symptomatic and fatal intracranial hemorrhage5. In the United States, less than 1% of patients presenting to community hospitals with acute ischemic stroke receive rtPA6. Inhibition of the final common pathway of platelet accumulation, via blockade of glycoprotein IIb/IIIa receptor-mediated platelet-platelet interactions, does reduce microvascular thrombosis in experimental stroke2. However, as with thrombolytic agents, small excesses of a GPIIb/IIIa receptor blocker culminated in serious intracerebral hemorrhage. It is therefore important to identify novel strategies for inhibition of platelet function in acute stroke that will reduce intravascular thrombosis without increasing risk of intracerebral hemorrhage.